The purpose of this project is to evaluate the carcinogenic potential of medical treatment with drugs. Since many cancer patients are exposed to both radiation and cytotoxic agents, these studies are a logical extension to the Branch's study of radiation-induced second cancers. In addition, other non-therapeutic drugs are studied when of special interest. The Branch also conducts studies of multiple primary cancers in order to generate hypotheses about host and environmental determinants of specific cancers. Populations under study include cancer patients reported to population-based cancer registries (especially the SEER Program), persons treated at major institutions, and those treated in randomized clinical trials. Additional details on collaborative projects can be found in Project No. ZOICPO4412-15 EEB, "Carcinogenic Effects of Therapeutic Drugs" and Project No. ZOICPO4410-15 EEB, "Studies of Persons at High Risk of Cancer." Breast cancer patients treated with alkylating agents had an increased risk of leukemia that depended on type of drug administered. Risk was highest for patients receiving the highest doses and for those treated with both radiotherapy and cytotoxic drugs. A cancer registry study found that chemotherapy for nonHodgkin's lymphoma was related to subsequent leukemia and bladder cancer. Anticonvulsive drugs used to treat epilepsy were not found to increase the overall risk of cancer, although slight increases in lung cancer and non-Hodgkin's lymphoma were noted. Children of epileptic mothers exposed to anti-convulsive drugs were not at increased risk of cancer. Children treated for retinoblastoma were found to be at very high risk of dying from a second cancer before reaching the age of 40 years, especially those with bilateral disease. Radiotherapy further increased the risk of second cancers, especially osteosarcomas. Radiotherapy for childhood cancer was linked to a high risk of thyroid cancer.